42. Mediastinal tumours and cysts, superior vena cava syndrome and mediastinal emphysema

1. Definition

• Mediastinal tumour or cyst → primary mass arising in the mediastinum, between the pleural sacs, from the sternum to the spine
• Superior vena cava (SVC) syndrome → symptoms from blocked venous return from the head, neck and arms through the SVC
• Mediastinal emphysema (pneumomediastinum) → free air in the mediastinum

2. Epidemiology

• Adults → thymoma, neurogenic tumours, cysts, germ cell tumours, lymphoma
• Children → neurogenic tumours, germ cell tumours, cysts, lymphoma; more often malignant
• Malignant → 25–50% of mediastinal masses in adults
• SVC syndrome → malignant in about 80% (lung cancer most often, then non-Hodgkin's lymphoma)
• Spontaneous pneumomediastinum → young men, 20–30 years

3. Aetiology and risk factors

Tumours and cysts

• Thymus → thymoma, thymic carcinoma, thymic hyperplasia (after chemotherapy, Graves'), thymic cyst
• Germ cells → teratoma, seminoma, non-seminomatous germ cell tumour (young men)
• Nerves → schwannoma, neurofibroma (neurofibromatosis), ganglioneuroma, neuroblastoma, paraganglioma
• Lymph nodes → Hodgkin's and non-Hodgkin's lymphoma, sarcoidosis, metastases
• Retrosternal goitre
• Foregut and mesothelial cysts → bronchogenic, oesophageal duplication, pericardial

SVC syndrome

• Malignant → lung cancer (small cell, right upper lobe), lymphoma, metastases, thymoma
• Benign → thrombosis around catheters and pacing leads (rising), fibrosing mediastinitis, goitre, aortic aneurysm

Pneumomediastinum

• Spontaneous → asthma, coughing, vomiting, Valsalva, labour, inhaled drugs
• Secondary → oesophageal or airway rupture, chest trauma, ventilation, dental or neck surgery

4. Pathogenesis

Compartments (key to diagnosis)

• Anterior (prevascular) → thymus, fat, nodes: the "4 Ts":
  • Thymoma
  • Teratoma and other germ cell tumours
  • "Terrible" lymphoma
  • Thyroid (retrosternal goitre)
• Middle (visceral) → heart, trachea, oesophagus, nodes: cysts, lymphoma, nodes
• Posterior (paravertebral) → sympathetic chain and nerves: neurogenic tumours

SVC syndrome

1. Tumour compresses, invades or thromboses the SVC
2. Venous pressure in the head and arms rises
3. Collaterals open → azygos, internal mammary, lateral thoracic, vertebral veins
4. Slow onset → collaterals compensate; fast onset → severe symptoms

Pneumomediastinum

• Macklin effect → alveoli rupture → air tracks along the bronchovascular sheaths to the hilum → mediastinum → neck, face and chest wall

5. Classification

Thymoma (WHO)

• Types A, AB, B1, B2, B3 → rising malignancy; thymic carcinoma (type C)
• Masaoka-Koga stage:
  • I → encapsulated
  • II → through the capsule into fat
  • III → into nearby organs (pericardium, lung, great vessels)
  • IVa → pleural or pericardial spread; IVb → lymph node or blood spread
• TNM 8th edition now also used

Germ cell tumours

• Mature teratoma → benign; hair, teeth, fat, calcium
• Seminoma → β-HCG may be mildly raised, AFP normal
• Non-seminomatous → AFP and β-HCG raised

Neurogenic tumours

• Nerve sheath → schwannoma (most common; Antoni A and B), neurofibroma, malignant nerve sheath tumour
• Ganglion cells → ganglioneuroma (benign, children) → ganglioneuroblastoma → neuroblastoma (malignant, infants)
• Paraganglia → paraganglioma, phaeochromocytoma (1% in the mediastinum)
• Dumbbell tumour → about 10% extend through the foramen into the spinal canal

Cysts (about 25% of masses)

• Pericardial cyst → "spring water" cyst at the right cardiophrenic angle
• Bronchogenic cyst → most common; near the carina
• Oesophageal duplication cyst, thymic cyst

6. Clinical picture

Symptoms

• Many → none; found on chest X-ray
• Mass effect → chest pain, cough, dyspnoea, stridor, dysphagia, hoarseness
• Myasthenia gravis → ptosis, diplopia, fatigable weakness: in about 40% of thymomas; 10–15% of myasthenia patients have a thymoma
• Other thymoma syndromes → pure red cell aplasia, hypogammaglobulinaemia
• Lymphoma → fever, night sweats, weight loss (B symptoms)
• Neurogenic → back pain, Horner's syndrome, cord compression (dumbbell)
• Phaeochromocytoma → hypertension, headache, sweating
• SVC syndrome:
  • Swelling of face, neck and arms; worse on bending or lying flat
  • Headache, dyspnoea, cough
  • Severe → stridor, confusion (cerebral oedema)
• Pneumomediastinum → sudden retrosternal pain, neck pain, dysphagia, change in voice

Signs

• SVC syndrome → distended neck and chest wall veins, facial plethora, cyanosis, arm oedema; Pemberton's sign with goitre
• Pneumomediastinum:
  • Subcutaneous emphysema → crepitus of the neck
  • Hamman's sign → crunch with each heartbeat

7. Diagnosis

Imaging

• Chest X-ray → widened mediastinum, mass, lateral film shows the compartment
• Contrast CT chest → test of choice: site, fat, calcium, cyst, invasion
• MRI → neurogenic tumours (spinal canal), cysts, vascular invasion
• PET-CT → lymphoma, malignant tumours
• SVC syndrome → contrast CT shows level, thrombus and collaterals
• Pneumomediastinum → chest X-ray: lucent lines along the heart, continuous diaphragm sign, thymic "sail" sign in children; CT if unclear
• Contrast swallow or endoscopy → exclude oesophageal rupture when there is vomiting, fever or effusion

Laboratory

• Tumour markers in every young man with an anterior mass → AFP, β-HCG, LDH
• Acetylcholine receptor antibodies → myasthenia
• Urinary or plasma metanephrines → paraganglioma
• Thyroid function → goitre

Tissue

• Thymoma, clear on CT and resectable → no biopsy; operate (biopsy can seed the pleura)
• Suspected lymphoma or germ cell tumour → CT-guided core biopsy, mediastinoscopy, anterior mediastinotomy (Chamberlain), VATS biopsy
• SVC syndrome → tissue diagnosis before steroids or radiotherapy if the patient is stable

8. Differential diagnosis

• Aortic aneurysm, vascular anomalies
• Hiatus hernia, achalasia (dilated oesophagus)
• Lymph node metastases (lung cancer), sarcoidosis, tuberculosis
• Pericardial fat pad
• Morgagni or Bochdalek hernia
• Pneumomediastinum versus pneumothorax, pneumopericardium

9. Treatment

Surgical

• Thymoma → complete resection (thymectomy with the whole thymus and fat):
  • Median sternotomy, or VATS or robotic approach for small, stage I–II tumours
  • Preserve both phrenic nerves
  • Myasthenia → control symptoms first; plasma exchange or IVIG before surgery
  • Stage III → en bloc resection of pericardium, lung or vessels; adjuvant radiotherapy
• Mature teratoma → complete resection
• Non-seminomatous germ cell tumour → cisplatin chemotherapy, then resect any residual mass
• Neurogenic tumour → resection, usually VATS; dumbbell tumour with a neurosurgeon (laminectomy first)
• Cysts → resect if symptomatic, growing or unclear; pericardial cysts may be watched
• Retrosternal goitre → usually through a neck incision; sternotomy rarely
• SVC syndrome, benign cause → surgical bypass or reconstruction if stenting fails

Conservative

• Lymphoma → chemotherapy, radiotherapy; no resection
• Seminoma → chemotherapy, radiotherapy
• SVC syndrome:
  1. Sit the patient up, oxygen
  2. Steroids for lymphoma or oedema, diuretics
  3. Endovascular stent → fastest relief; first choice for severe symptoms
  4. Radiotherapy or chemotherapy for the cause (chemotherapy for small cell cancer and lymphoma)
  5. Thrombosis → anticoagulation, catheter-directed thrombolysis, remove the catheter
• Pneumomediastinum:
  • Spontaneous → rest, analgesia, oxygen, avoid Valsalva; resolves in days
  • Secondary → treat the cause (perforation → see mediastinitis)
  • Tension pneumomediastinum (rare) → decompression

10. Complications

• Tumour → invasion of SVC, pericardium, phrenic and recurrent laryngeal nerves; airway collapse under anaesthesia
• Large anterior mass → airway and cardiac collapse at induction of general anaesthesia
• Thymectomy → myasthenic crisis, phrenic nerve palsy, bleeding
• SVC syndrome → cerebral oedema, laryngeal oedema, thrombosis
• Pneumomediastinum → pneumothorax, pneumopericardium (rare)

11. Prognosis

• Thymoma → 10-year survival about 90% (stage I) to under 50% (stage IV)
• Mature teratoma, schwannoma → cured by resection
• SVC syndrome → depends on the cause; median survival with cancer often < 1 year